Correlation between protective immunity to alpha-synuclein aggregates, oxidative stress and inflammation

Gruden, Marina A., Yanamandra, Kiran, Kucheryanu, Valery G., Bocharova, Olga R., Sherstnev, Vladimir V., Morozova-Roche, Ludmilla A. and Sewell, Robert David Edmund 2012. Correlation between protective immunity to alpha-synuclein aggregates, oxidative stress and inflammation. Neuroimmunomodulation 19 (6) , pp. 334-342. 10.1159/000341400

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Abstract

Objective: Protein aggregation leading to central amyloid deposition is implicated in Parkinson’s disease (PD). During disease progression, inflammation and oxidative stress may well invoke humoral immunity against pathological aggregates of PD-associated α-synuclein. The aim was to investigate any possible concurrence between autoimmune responses to α-synuclein monomers, oligomers or fibrils with oxidative stress and inflammation. Methods: The formation of α-synuclein amyloid species was assessed by thioflavin-T assay and atomic force microscopy was employed to confirm their morphology. Serum autoantibody titers to α-synuclein conformations were determined by ELISA. Enzyme activity and concentrations of oxidative stress/inflammatory indicators were evaluated by enzyme and ELISA protocols. Results: In PD patient sera, a differential increase in autoantibody titers to α-synuclein monomers, toxic oligomers or fibrils was associated with boosted levels of the pro-inflammatory cytokine interleukin-6 and tumour necrosis factor-α, but a decrease in interferon-γ concentration. In addition, levels of malondialdehyde were elevated whilst those of glutathione were reduced along with decrements in the activity of the antioxidants: superoxide dismutase, catalase and glutathione transferase. Conclusions: It is hypothesized that the generation of α-synuclein amyloid aggregates allied with oxidative stress and inflammatory reactions may invoke humoral immunity protecting against dopaminergic neuronal death. Hence, humoral immunity is a common integrative factor throughout PD progression which is directed towards prevention of further neurodegeneration, so potential treatment strategies should attempt to maintain PD patient immune status.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Pharmacy
Subjects:	R Medicine > RS Pharmacy and materia medica
Uncontrolled Keywords:	Parkinson’s disease; α-Synuclein oligomers; autoantibodies; cytokines; oxidative stress.
Publisher:	Karger
ISSN:	1021-7401
Date of Acceptance:	15 June 2012
Last Modified:	19 Sep 2017 12:50
URI:	https://orca.cardiff.ac.uk/id/eprint/70527

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